Kidney Week

Abstract: SA-PO0285

Atypical Cadherin FAT1 Protects Against Phosphate-Induced Calcification in Vascular Smooth Muscle Cells

Session Information

• Bone and Mineral Metabolism: Basic Research
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 501 Bone and Mineral Metabolism: Basic

Authors

• Oteyola, Ayodeji Ojo, Albert Einstein College of Medicine, New York, New York, United States

Ayodeji Ojo Oteyola, MSc, PhD

• Quintar, Amado, Albert Einstein College of Medicine, New York, New York, United States

Amado Quintar, DrMed, PhD

• Chan, Bailey, Albert Einstein College of Medicine, New York, New York, United States

Bailey Chan

• Abdelaal, Shadi A., Albert Einstein College of Medicine, New York, New York, United States

Shadi A. Abdelaal, MD

• Riascos-Bernal, Dario F., Albert Einstein College of Medicine, New York, New York, United States

Dario F. Riascos-Bernal, MD, PhD

• Ross, Michael J., Albert Einstein College of Medicine, New York, New York, United States

Michael J. Ross, MD, FASN

• Sibinga, Nicholas, Albert Einstein College of Medicine, New York, New York, United States

Nicholas Sibinga, MD

• Chen, Wei, Albert Einstein College of Medicine, New York, New York, United States

Wei Chen, MD, MS, FASN

Background

The Vascular smooth muscle cell (VSMC) is the key cell type in the pathogenesis of vascular calcification, a common problem that contributes to mortality in patients with CKD. The Atypical cadherin FAT1, a transmembrane protein, regulates proliferation and migration of VSMCs, but whether FAT1 affects vascular calcification is unexplored. We hypothesized that FAT1 limits phosphate-induced calcification in VSMCs.

Methods

First, we assessed calcification using von Kossa staining in brachial artery biopsies from patients with ESKD who underwent arterio-venous access surgery and compared FAT1 expression between calcified (n=4) and non-calcified arteries (n=3) using immunofluorescence. Then, we treated mouse aortic ring ex vivo with high phosphate (3mM and 3.5mM) and evaluated calcification and FAT1 expression. Lastly, we compared phosphate-induced calcification in FAT1 knockout (KO) mouse VSMCs vs. controls. FAT1KO VSMCs were harvested from the aorta of FAT1^loxP/loxPTagln-cre mice. VSMCs in culture were exposed to normal phosphate (0.9 mM) and high phosphate (3 mM and 3.5 mM) and calcification was quantified using Alizarin Red staining.

Results

FAT1 expression was lower in calcified brachial arteries from ESKD patients compared to non-calcified controls (p=0.04; fig. a). In ex-vivo mouse aortic rings, treatment with high phosphate induced calcification (p=0.03) and resulted in lower FAT1 expression compared to those treated with normal phosphate, with a statistically notable trend (p for trend =0.07; fig. b). Western Blot confirmed the loss of FAT1 in FAT1KO mouse VSMCs (fig. c); and compared to controls, FAT1KO mouse VSMCs had higher phosphate-induced calcification with p=0.03 and p=0.007 for 3mM and 3.5 mM phosphate, respectively (fig. d).

Conclusion

Our findings support the clinical relevance of FAT1 in vascular calcification associated with CKD and suggest a protective role of FAT1 against phosphate-induced vascular calcification. Our future work will involve validating these results in vivo and studying underlying mechanisms.

Funding

• Other NIH Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20259jq4qxwh